Indapamide Alkaloid - instructions for use, dose, side effects, contraindications

Core: lactose monohydrate 129,50 mg; (low-viscosity hydroxyethylcellulose) 6.00 mg, hyethelose (hydroxyethyl cellulose (high viscosity) 60.00 mg, silicon dioxide colloid 2.00 mg, magnesium stearate 1.00 mg.

Shell: giprolose 6,01 mg; titanium dioxide 3.99 mg.

Description:

Round, biconvex tablets, covered with film shell white or almost white. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Indapamide, a sulfonamide derivative containing an indole ring, is an antihypertensive drug. According to its pharmacological properties, it is close to thiazide diuretics, whose action is related to inhibition of the reverse absorption of sodium ions in the cortical segment of the nephron loop. Indapamide increases the excretion of urine ions of sodium, chlorine and, to a lesser extent, potassium and magnesium ions, which is accompanied by increased diuresis. Vasodilator effects and reduction of total peripheral vascular resistance (OPSS) are based on the following mechanisms: a decrease in the reactivity of the vascular wall to norepinephrine and angiotensin II; an increase in the synthesis of prostaglandins with vasodilating activity; oppression of calcium current in the smooth-muscle walls of blood vessels.

Indapamide reduces the severity of left ventricular hypertrophy of the heart.

In therapeutic doses, it has no effect on lipid and carbohydrate metabolism (including in patients with concomitant diabetes mellitus).

Thiazide and thiazide-like diuretics at a certain dose reach a plateau of therapeutic effect, while the severity of unwanted effects continues to increase.If the desired therapeutic effect can not be achieved, further dose increases are not advisable.

Pharmacokinetics:

The drug is available in the form of a film-coated tablet, with prolonged release of indapamide in the gastrointestinal tract (GI tract).

Suction

The released indapamide quickly and completely absorbed into the digestive tract. The intake of food slightly increases the time of absorption of the drug, without affecting the completeness of absorption. The maximum concentration in the blood plasma is achieved 12 hours after ingestion of a single dose. With repeated administration of fluctuations in the concentration of indapamide in the blood plasma in the interval between doses of two doses are smoothed. There is an individual variability in the absorption of the drug. Distribution

The binding to plasma proteins is about 79%. Equilibrium concentration is achieved after 7 days of regular intake. When again taking indapamide, there is no cumulation.

Metabolism and excretion

Indapamide is biotransformed and is excreted as inactive metabolites, mainly through the kidneys - 70% and through the intestines - 22%.The half-life is 14-24 hours (an average of 18 hours).

Pharmacokinetics in special clinical cases

In patients with renal insufficiency, the pharmacokinetic parameters do not change.

Indications:

Arterial hypertension.

Contraindications:

Hypersensitivity to indapamide, other derivatives of sulfonamide or to any of the components of the drug.

Renal failure of severe degree (creatinine clearance less than 30 ml / min).

Severe liver dysfunction or hepatic encephalopathy.

Hypokalemia.

Acute disturbance of cerebral circulation.

Pregnancy, the period of breastfeeding.

Age to 18 years (effectiveness and safety not established).

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the preparation contains lactose).

Carefully:

Violation of the function of the liver and kidneys, violation of water-electrolyte balance. Diabetes mellitus, hyperuricemia and gout, hyperparathyroidism. Use in patients with an increased interval QT on ECG, in weakened patients or receiving simultaneously antiarrhythmic drugs or drugs that can increase the interval QT (cm.section "Interactions with other drugs").

Pregnancy and lactation:

During pregnancy, do not prescribe diuretic drugs. Do not use these drugs to treat physiological swelling in pregnancy. Diuretic drugs can cause fetoplacental ischemia and lead to impaired fetal development. Use of the drug Indapamide Alkaloid is contraindicated during pregnancy.

Due to indapamide excreted in breast milk, the use of the drug during breast-feeding is not recommended.

Dosing and Administration:

Inside, 1 tablet a day, preferably in the morning. The tablet should be swallowed whole, not liquid, squeezed with water.

If after 4-8 weeks of treatment the desired therapeutic effect is not achieved, then do not increase the dose of the drug (the diuretic effect increases and the risk of side effects increases without amplification antihypertensive effect), another antihypertensive drug that is not a diuretic should be added to the treatment.

Thiazide and thiazide-like diuretics are effective only with normal kidney function or with minimal disturbances.Indapamide Alkaloid can be used in elderly patients with normal or slightly impaired renal function.

Side effects:

The incidence of side effects that may be caused by thiazide-like diuretics, including indapamide, is given in accordance with the classification of the World Health Organization: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10 000); frequency (frequency can not be calculated from available data).

From the blood and lymphatic system: very rarely - thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

From the central nervous system: rarely - asthenia, headache, paresthesia, vertigo; Unspecified frequency - fainting.

From the cardiovascular system: very rarely - arrhythmia, marked decrease in blood pressure; Unspecified frequency - polymorphic ventricular tachycardia of the "pirouette" type (possibly with fatal outcome), (see sections "Interaction with other medicinal products" and "Special instructions").

From the digestive system: infrequently - vomiting; rarely - nausea, constipation, dryness of the oral mucosa; very rarely - pancreatitis.

From the urinary system: very rarely - renal failure.

From the liver and bile ducts: very rarely - a violation of liver function; unspecified frequency - the possibility of developing hepatic encephalopathy in the case of liver failure (see Sections "Contraindications" and "Special instructions"); hepatitis.

From the skin and subcutaneous fat: reactions of hypersensitivity, mainly dermatological, in patients with a predisposition to allergic and asthmatic reactions: often - maculopapular rash; infrequently - hemorrhagic vasculitis; very rarely - angioedema and / or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; Unspecified frequency - in patients with acute form of systemic lupus erythematosus, the course of the disease may worsen; cases of photosensitivity reactions are described (see Sections "Special instructions" and "Interaction with other medicinal products").

Laboratory indicators:

Unspecified frequency: interval increase QT on the ECG (see section "Special instructions"); increased concentration of uric acid and glucose in the blood; increased activity of "liver" transaminases.

Very rarely: hypercalcemia.

Unspecified frequency: decrease in potassium content and development hypokalemia, especially significant for patients at risk (see section "Special instructions"); hyponatremia, accompanied by hypovolemia, dehydration and orthostatic hypotension. Simultaneous hypochloraemia can lead to metabolic alkalosis of compensatory nature (the probability and severity of this effect is low).

Overdose:

Indapamide even in very high concentrations (up to 40 mg, i.e. 27 times more than the therapeutic dose) does not have a toxic effect. Symptoms of acute poisoning The drug is primarily associated with a violation of the water-electrolyte balance (hyponatremia, hypokalemia). Nausea, vomiting, decreased blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria, or oliguria, leading to anuria (due to hypovolemia) may also occur.

Treatment: urgent measures aimed at removing the drug from the body: gastric lavage and / or the appointment of activated charcoal, followed by the restoration of normal water-electrolyte balance.

Interaction:

Not recommended combinations

Lithium preparations

With simultaneous use of indapamide and lithium preparations, an increase in the concentration of lithium in blood plasma can be observed due to a decrease in its excretion, accompanied by the appearance of signs of an overdose. If necessary, diuretic drugs can be used in combination with lithium preparations, while carefully selecting the dose of drugs, constantly monitoring the lithium content in blood plasma.

Combinations that require special control

Preparations that can cause a polymorphic ventricular tachycardia such as "pirouette"

- antiarrhythmic drugs of class I A (quinidine, hydroquinidine, disopyramide);

- antiarrhythmic drugs of class III (amiodarone, dofetilide, ibutilide) sotalol;

- some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);

- other: bepridil, cisapride, difemanyl, erythromycin (intravenously), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, wincamine (intravenously).

Hypokalemia increases the risk of developing ventricular arrhythmias, especially polymorphic ventricular tachycardia such as pirouette. It is necessary to determine the level of potassium in the blood plasma and, if necessary, adjust it before starting the combination therapy with indapamide and the above drugs. It is necessary to monitor the clinical state of the patient, control the level of electrolytes of blood plasma, ECG parameters.

Patients with hypokalemia should use drugs that do not cause polymorphic ventricular tachycardia such as pirouette.

Non-steroidal anti-inflammatory drugs (NSAIDs) (for systemic administration), including selective inhibitors of cyclooxygenase-2 (COX-2), high doses of acetylsalicylic acid (≥ 3 g / day)

It is possible to reduce the antihypertensive effect of indapamide. With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration). Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.

Angiotensin-converting enzyme (PS) inhibitors

The use of ACE inhibitors in patients with a reduced concentration of sodium ions in the blood,increases the risk of sudden arterial hypotension and / or acute renal failure (especially with renal artery stenosis). Patients with hypertension and reduced by the intake of diuretics with the content of sodium ions in blood plasma should:

- 3 days before the start of treatment with ACE inhibitors, stop taking diuretics. In the future, if necessary, taking diuretics to resume;

- or start therapy with ACE inhibitors from low, gradually increasing doses.

In chronic heart failure, treatment with ACE inhibitors should begin with low doses with the possible preliminary reduction of doses of diuretics. In all cases, in the first week of taking ACE inhibitors, kidney function (creatinine content in the blood plasma) should be monitored.

With the simultaneous use of indapamide with other drugs that can cause hypokalemia, incl. from amphotericin B (intravenously), gluco- and mineralocorticoids (for systemic administration), tetracosactide, laxatives stimulating intestinal peristalsis, the risk of developing hypokalemia due to the additive effect increases (constant monitoring of the level of potassium in the blood plasma and, if necessary, appropriate treatment) is required.It is recommended to use laxatives that do not stimulate intestinal motility.

With the simultaneous use of indapamide with baclofen there is a growing anti-hypertensive effect (necessary to compensate for the loss of water and at the beginning of treatment carefully monitor renal function). When used simultaneously with cardiac glycosides possible development of hypokalemia and increased toxic effect of cardiac glycosides (need to monitor the level of potassium in the blood plasma, and ECG and adjust therapy as needed).

Combinations that require special attention

Potassium-sparing diuretics (amiloride, spironolactone, triamterene) Combination therapy with indapamide and potassium-sparing diuretics suitable for some patients, but it does not exclude the possibility of hypokalemia (especially in patients with diabetes and renal insufficiency) or hyperkalemia.

It is necessary to monitor the potassium content in the blood plasma, the parameters of the ECG and, if necessary, adjust the therapy.

Metformin

Functional renal failure, which can occur against the background of diuretics,especially "loop", with the simultaneous use of metformin increases the risk of lactic acidosis.

Do not assign metformin, if the creatinine concentration exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

Iodine-containing contrast agents

Dehydration of the body against the background of taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents.

Before using iodine-containing contrast agents, patients must compensate for fluid loss.

Tricyclic antidepressants, antipsychotic drugs (cheiroleptic iki)

Preparations of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

Salts of calcium

With simultaneous application, the development of hypercalcemia is possible, due to a decrease in excretion of calcium ions by the kidneys.

Cyclosporin, tacrolimus

It is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine, even with a normal content of liquid and sodium ions.

Corticosteroids, tetracosactide (with systemic application)

Reduction of antihypertensive action (fluid retention and sodium ions due to the action of corticosteroids).

Special instructions:

Dysfunction of the liver

In patients with impaired liver function, therapy with thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy, especially in the case of disturbance of the water-electrolyte balance. In this case, the drug should be discontinued immediately. Photosensitivity

Against the background of taking thiazide and thiazide-like diuretics, cases of development of photosensitivity reactions were reported (see Section "Adverse reactions"). In the case of developing photosensitivity reactions against the background of taking the drug should stop treatment. If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Water-electrolyte balance:

Content of sodium ions in blood plasma:

Before starting therapy with the drug Indapamide Alkaloid it is necessary to determine the content of sodium ions in the blood plasma.Against the background of taking the drug may develop hyponatremia, sometimes, with serious consequences. Decrease in the content of sodium ions in the blood plasma initially can be asymptomatic, therefore regular monitoring is necessary. In the treatment of elderly patients and patients with cirrhosis of the liver, the content of sodium ions in the blood should be determined more often.

The content of potassium ions in the blood plasma:

Therapy with the drug Indapamide Alkaloid can cause a sharp drop in potassium in the blood plasma and the development of hypokalemia. In the treatment of patients at risk (elderly patients who are weakened or are receiving concomitant drug therapy with other antiarrhythmic drugs and drugs that may increase the interval QT, patients with cirrhosis of the liver, peripheral edema or ascites, ischemic heart disease, patients with heart failure) it is necessary to prevent hypokalemia. In such patients, hypokalemia contributes to cardiotoxicity of cardiac glycosides and increases the risk of heart rhythm disturbances. Patients with an enlarged interval QT (it does not matter whether this increase is due to innate causes or effects of medicines) also fall into the category of risk.

Hypokalemia, as well as bradycardia, is a condition that contributes to the development of severe arrhythmias and, especially, polymorphic ventricular pirouette tachycardia that can lead to death. In all the cases described above, it is necessary to regularly monitor the content of potassium ions in the blood plasma. the concentration of potassium ions in the blood should be performed within the first week after the initiation of treatment with the drug Indapamide Alkaloid, the detection of hypokalemia requires appropriate correction.

Calcium in the blood plasma:

It should be borne in mind that the preparation Indapamide Alkaloid can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the concentration of calcium in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism. It is necessary to cancel the reception of Indapamide Alkaloid before the study of parathyroid function.

The content of glucose in the blood plasma

It is necessary to monitor the blood glucose level in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

Patients with gout may increase the incidence of attacks or exacerbation of the disease.

Diuretic drugs and kidney function

The drug Indapamide Alkaloid is effective only in patients with normal or slightly impaired renal function (plasma creatinine content in adults below 25 mg / L or 220 μmol / L). In elderly patients, the threshold value of creatinine concentration in the blood plasma varies depending on age, body weight and gender. At the beginning of treatment, there may be a decrease in glomerular filtration rate due to hypovolemia, which in turn is caused by loss of fluid and sodium ions on the background of taking diuretic drugs. As a consequence, in a plasma blood levels of urea and creatinine may increase. In patients with normal function, such transient functional renal failure usually passes without consequences.

Athletes

Indapamide Alkaloid can give a positive result in the conduct of doping control in athletes.

The preparation contains lactose. Indapamide Alkaloid is contraindicated in patients with congenital lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Effect on the ability to drive transp. cf. and fur:

During the treatment with the drug Indapamide Alkaloid caution (risk of dizziness, drowsiness) in the management of vehicles and other potentially hazardous activities that require increased concentration and speed of psychomotor reactions should be taken.

Form release / dosage:

Tablets with prolonged release, film-coated 1.5 mg.

Packaging:

Primary packaging: 10 tablets per blister perforated from aluminum foil and PVC / PVDC film.

Secondary packaging: 3 blisters (30 tablets), along with instructions for use, are placed in a cardboard box.

Storage conditions:

Store in original packaging at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004081

Date of registration:16.01.2017

Expiration Date:16.01.2022

The owner of the registration certificate:Alkaloid, JSCAlkaloid, JSC Macedonia

Manufacturer: & nbsp

ALKALOID, AD Macedonia

Representation: & nbspALKALOID, AOALKALOID, AO

Information update date: & nbsp30.01.2017

Illustrated instructions

Instructions

Indapamide Alkaloid (Indapamide Alkaloid)